Medical devices used for patient treatment can be a source of microbial (bacterial or fungal) infection in such patients. For example, insertion or implantation of a catheter into a patient can introduce microbes and/or, when left in place for prolonged periods of time, permit the introduction of microbes during long-term exposure of the catheter exit site to the environment. In addition, long-term catheter use often produces a biofilm on the catheter surface, which facilitates the development of infection that can cause patient discomfort and compromise patient health.
Microbial infection may be prevented by bonding an antimicrobial agent to a medical device. For example, U.S. Pat. No. 5,476,509 describes a catheter having a polymeric coating that has an antibiotic agent covalently or ionically bound thereto. Similarly, U.S. Pat. No. 5,798,115 describes a catheter having a polymer coating that has an antibiotic covalently bound to the polymer backbone. Bacteria kept in contact with these catheters for prolonged periods of time may be killed. However, these catheters are not effective at killing bacteria introduced into the body during insertion of the catheter. Because the antibiotic is attached to the catheter, the bacteria are able to migrate away from the catheter to avoid the antibiotic effect.
An antimicrobial catheter that is coated with a matrix-forming polymer in which an antibiotic agent is incorporated in the polymer coating is described in U.S. Pat. No. 5,019,096. Because the antibiotic is not covalently bound to the polymer, it is able to diffuse away from the catheter to attack organisms in the surrounding area.
However, the incorporation of antimicrobial agents into medical device coatings via insoluble particles (i.e., particles that are not soluble in the solvents used to coat the medical device) has produced unsatisfactory results, especially when dip or spray coating techniques are used to coat medical devices. For example, the insoluble antimicrobial particles tend to settle out from the solution used during coating. When particles settle from the solution, the concentration of the antimicrobial particles in the resulting coating is reduced over time during manufacturing, thereby reducing the manufacturer's ability to control the antimicrobial agent concentration on the device.
In addition, the antimicrobial particles can agglomerate in the coating solution into larger particles (from sizes of less than 4 microns to sizes from 10 to 100 microns or more). This can produce particles that are large enough to be felt on the surface of a coated device, and, if large enough, these agglomerated particles can produce patient discomfort. For example, particles larger than about 50 microns can usually be felt by a patient upon insertion of a Foley catheter into the urethra.
Particles smaller than 50 microns can also create problems. Although smaller particles in the range of 10 to 50 microns are not readily felt by patients, microscopic examination reveals that these particles produce coating surfaces that are bumpy or micro-rough. A micro-rough surface has a higher surface area than a smooth coated surface and this tends to increase the attachment of bacteria and other microorganisms. The increased surface area for microbial attachment and increased tissue irritation due to a rough catheter surface significantly reduces the ability of the antimicrobial coating to fight infection. Thus, there is a need for negating the potentially adverse effects that insoluble antimicrobial particle agglomeration can have on the performance of a coated medical device.
The problems associated with insoluble antimicrobial particles are especially relevant to antimicrobial coatings applied to catheters and, in particular, to Foley catheters.